The thermodynamic properties of both small nonelectrolytes and proteins in salt solutions will be investigated in order to elucidate the mechanism of interaction of salts with proteins. Free energies and enthalpies of transfer of the nonelectrolytes and proteins will be determined by isopiestic and calorimetric methods. Combination of the values obtained for the model compounds with the protein data give a measure of the accessibility of the groups in the protein to the solvent. In addition, the nature and number of the groups exposed to the solvent as the protein unfolds will be assessed. Structural studies will also be carried out in protein-salt systems. The methods which will be utilized include circular dichroism spectroscopy and Raman spectroscopy. The objective of this work is to provide direct proof of the interactions postulated from the thermodynamic data. The classification and sorting out of the different ionic effects on proteins will provide information regarding the conformational stability to biopolymers. In addition, these results will help elucidate the mechanisms of accumulation of ions and their transport in biological systems.